Adoptive immunotherapy is considered a promising strategy for the treatment of metastatic tumors and current research efforts
are directed to define the optimal approach and facilitate the transferability from preclinical to clinical settings. Among several approaches
it is possible to schematically distinguish strategies based on either MHC-restricted or MHC-unrestricted immune effectors. The first are
mainly based on the infusion of tumor-specific T lymphocytes capable of recognizing determined MHC-restricted tumor associated
antigens (TAA) through their T cell receptor. MHC-unrestricted approaches do not target specific tumor associated antigens and are
mainly mediated by effectors of the innate immune system, like natural killer (NK) cells or NKT cells, first barrier against pathogens and
tumorigenesis processes, or by ex vivo activated lymphocytes like cytokine-induced killer (CIK) cells. MHC-unrestricted effectors are
usually more abundant than TAA-specific precursors and easier to expand. Furthermore their activity is not restricted to precise HLAhaplotypes,
not limited to a single tumor histotype and could overcome downregulation of MHC molecules operated by tumor cells as
immune escape mechanism.
In this review we will discuss the main cancer immunotherapy strategies based on MHC-unrestricted immune effectors. The topic will be
approached from the angle of ex vivo expansion protocols in clinical prospective, as well as potential approaches to favorably modulate
Keywords: Adoptive immunotherapy, MHC-unrestricted activity, NK, CIK, NKT.
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